Lenalidomide, an analog of Thalidomide, is a kind of immunomodulator with anti-vascular proliferation and anti-tumor activities; its chemical name is 3-(4-amino-1-oxo-1,3-dihydro-2H-isoindol-2-yl)-2,6-dioxopiperidine and its chemical structure is as following:

Lenalidomide has the residue of dioxopiperidine and dihydroisoindoline residue, as well as an asymmetric center in its structure. At present Lenalidomide approved on the market are racemic mixtures.
As is manifest in the article “Amino-substituted thalidomide analogs: Potent inhibitors of TNF-α production” (Bioorganic & Medicinal Chemistry Letters, Vol. 9, Issue 11, 7 Jun. 1999, pp 1625-1630) and the Chinese Patent ZL97180299.8 by Muller etc., the method of preparing 3-(substituted dihydroisoindolinone-2-yl)-2,6-dioxopiperidine is as following: α-aminoglutarimide hydrochloride reacts with methyl 2-bromomethyl-3-nitrobenzoate, then hydrogenated over Pd/C to yield lenalidomide.

wherein, (a) under ultraviolet light (mercury lamp), NBS, CCl4, refluxing; (b) Et3N, DMF, 80° C.; (c) H2, 10% Pd/C, MeOH. 7a X=4-NO2, 8a X=4-NH2. In which, the synthesis of α-aminoglutarimide hydrochloride begins with N-benzyloxycarbony-L-glutamine which reacts with N,N′-carbonyldiimidazole (CDI) refluxing in THF to yield N-benzyloxycarbony-aminoglutarimide; the key material of the reaction is: methyl 2-bromomethyl-3-nitro benzoate, which is converted from 2-methyl-3-nitrobenzoate by catalytic bromination in the condition of carbon tetrachloride under ultraviolet light. The catalytic and refluxing reaction needs long time and the yield is low. Additionally, the mass production is unease to be realized due to the difficulty of workers' labour protection against ultraviolet produced by mercury lamp as catalytic light source.
In the US Patent application US2006/0052609 A1, Muller etc. disclosed another synthetic method of 3-(substituted dihydroisoindolinone-2-yl)-2,6-dioxopiperidine:

In the US Patent application US2006052609A1 and the Chinese Patent application CN97180299.8, the reaction product was purified by column chromatography at least twice or more, which made industrial operation complicated and made it difficult to industrial scale-up production.
In the US Patent application US2006052609A1 and the Chinese Patent application CN97180299.8, pressurized hydrogenation was both utilized twice, which was of much more risk in industrial operation.
In addition, when N-benzyloxycarbony-L-glutamine, as initial material, reacted with N,N′-carbonyldiimidazole in THF refluxing for 24 h to yield N-benzyloxycarbony-aminoglutarimide, low purity of yield due to long reactive time for refluxing and high temperature made extraction difficult.
On the other hand, the total yield was lower than 20% and 18% respectively reported in the US Patent application US2006052609A1 and the Chinese Patent application. Also, in the above two documents “lethal carbon tetrachloride” was reported to be reactive solvent used for refluxing. Carbon tetrachloride had serious destruction to ozone layer, which was forbidden to use by UNEP. Because of the high toxicity of carbon tetrachloride, it was difficult to dispose this substance, which is harmful to environment.